title: Hyperinsulinemia and skeletal muscle fatty acid trafficking.
abstract: We hypothesized that insulin alters plasma free fatty acid (FFA) trafficking into intramyocellular (im) long-chain acylcarnitines (imLCAC) and triglycerides (imTG). Overnight-fasted adults (n = 41) received intravenous infusions of [U-¹³C]palmitate (0400-0900 h) and [U-¹³C]oleate (0800-1400 h) to label imTG and imLCAC. A euglycemic-hyperinsulinemic (1.0 mU·kg fat-free mass⁻¹·min⁻¹) clamp (0800-1400 h) and two muscle biopsies (0900 h, 1400 h) were performed. The patterns of [U-¹³C]palmitate incorporation into imTG-palmitate and palmitoylcarnitine were similar to those we reported in overnight postabsorptive adults (saline control); the intramyocellular palmitoylcarnitine enrichment was not different from and correlated with imTG-palmitate enrichment for both the morning (r = 0.38, P = 0.02) and afternoon (r = 0.44, P = 0.006) biopsy samples. Plasma FFA concentrations, flux, and the incorporation of plasma oleate into imTG-oleate during hyperinsulinemia were ~1/10th of that observed in the previous saline control studies (P < 0.001). At the time of the second biopsy, the enrichment in oleoylcarnitine was <25% of that in imTG-oleate and was not correlated with imTG-oleate enrichment. The intramyocellular nonesterified fatty acid-palmitate-to-imTG-palmitate enrichment ratio was greater (P < 0.05) in women than men, suggesting that sex differences in intramyocellular palmitate trafficking may occur under hyperinsulinemic conditions. We conclude that plasma FFA trafficking into imTG during hyperinsulinemia is markedly suppressed, and these newly incorporated FFA fatty acids do not readily enter the LCAC preoxidative pools. Hyperinsulinemia does not seem to inhibit the entry of fatty acids from imTG pools that were labeled under fasting conditions, possibly reflecting the presence of two distinct imTG pools that are differentially regulated by insulin.
authors.affiliation: Mayo Clinic, Rochester, Minnesota;
authors.forename: Jill A
authors.initials: JA
authors.lastname: Kanaley
authors.forename: Samyah
authors.initials: S
authors.lastname: Shadid
authors.forename: Michael T
authors.initials: MT
authors.lastname: Sheehan
authors.forename: ZengKui
authors.initials: Z
authors.lastname: Guo
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jensen
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D015331:Cohort Studies; D015536:Down-Regulation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D019308:Palmitic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D010172:Palmitoylcarnitine / Q000378:metabolism; D012727:Sex Characteristics; D014280:Triglycerides / Q000378:metabolism; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; C026968:oleoylcarnitine; D010172:Palmitoylcarnitine; D019301:Oleic Acid; D019308:Palmitic Acid; D002331:Carnitine
keywords: isotopic tracers; long-chain acylcarnitines; nonesterified fatty acids